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Hemolysis, interference and delta checks

15 min

  • Distinguish collection hemolysis from possible hemolysis in the patient
  • Distinguish a patient-related interference from a collection problem
  • Check identity, contamination, and the run behind a failed delta check before release

Read the full reference

Try first

Try first

After a difficult syringe draw through a small needle, a serum specimen is red and its hemolysis index is far above the potassium limit. The potassium reads 6.0 mmol/L. The care team asks whether the patient is hemolyzing. What does this specimen tell you?

The next section explains it.

The next section explains it.

Right. The next section explains why.

The next section explains it.

Get the idea

A flawed specimen raises two questions before the number itself:

  • whether the problem started in the tube or in the patient
  • whether a new specimen will fix it

Hemolysis from the draw

Most hemolyzed specimens are damaged during collection or handling:1,2

  • a needle too narrow for the flow
  • hard pulling on a syringe, or forcing blood into a tube
  • shaking a tube that needs gentle inversion
  • drawing before the antiseptic has dried

Broken red cells release potassium, LDH and AST into the serum, and free hemoglobin disturbs optical readings. Those changes belong to the specimen. A tube hemolyzed during the draw cannot show whether red cells are breaking down in the patient, however high its LDH.2,3

Hemolysis in the patient

When red cells break inside the circulation, every specimen shows it, including a carefully collected one. A properly collected specimen answers the question:3,4

  • Low haptoglobin, raised indirect bilirubin and a rising reticulocyte count point to hemolysis in the patient.
  • A specimen that comes back hemolyzed again after a clean venipuncture points the same way.

Where each problem starts

FindingWhere it startsWill a redraw fix it?
Hemolysis from a difficult drawThe tubeUsually, with careful collection
Hemolysis in the patientThe patientNo
IcterusThe patient's bilirubinNo
Lipemia after a mealA recent mealOften, with a fasting specimen
Lipemia from severe hypertriglyceridemiaThe patient's lipidsNo

Interference from the patient

Bilirubin and lipid that come from the patient appear in the next specimen too, so a redraw repeats the problem and delays the result. The laboratory works on the tube it has:5,6

  • the method's index limits
  • a blank
  • a validated alternate method
  • for lipemia, ultracentrifugation

A failed delta check

A delta check compares a result with the patient's previous one and flags a change larger than the laboratory's limit.7 Any of these can cause it:

  • a real change in the patient
  • a specimen from another patient
  • contamination, such as infusion fluid
  • a problem in the run

Before release:

  • Confirm identity against the label and the collection record.
  • Look for contamination.
  • Check the run.

A large change in a result that barely moves within one person, such as MCV, points strongly at a specimen from the wrong patient.7

References
  1. Simundic AM, Bölenius K, Cadamuro J, et al. Joint EFLM-COLABIOCLI recommendation for venous blood sampling. Clin Chem Lab Med. 2018;56(12):2015-2038. doi:10.1515/cclm-2018-0602
  2. Simundic AM, Baird G, Cadamuro J, Costelloe SJ, Lippi G. Managing hemolyzed samples in clinical laboratories. Crit Rev Clin Lab Sci. 2020;57(1):1-21. doi:10.1080/10408363.2019.1664391
  3. Keohane EM, Preston MM, Mirza KM, Walenga JM, eds. Rodak's Hematology: Clinical Principles and Applications. 7th ed. Elsevier; 2025.
  4. Krasowski MD. Educational case: hemolysis and lipemia interference with laboratory testing. Acad Pathol. 2019;6:2374289519888754. doi:10.1177/2374289519888754
  5. Nikolac N. Lipemia: causes, interference mechanisms, detection and management. Biochem Med (Zagreb). 2014;24(1):57-67. doi:10.11613/BM.2014.008
  6. Clinical and Laboratory Standards Institute. Hemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators of Interference in Clinical Laboratory Analysis. CLSI document C56-A. Clinical and Laboratory Standards Institute; 2012.
  7. Clinical and Laboratory Standards Institute. Use of Delta Checks in the Medical Laboratory. 2nd ed. CLSI guideline EP33. Clinical and Laboratory Standards Institute; 2023. Accessed September 23, 2026.

Watch one

An emergency department nurse sends a potassium drawn from a hand vein through a 25-gauge needle on a syringe. The blood came slowly, so the nurse pulled hard on the plunger, then pushed the blood back through the needle into the tube. Your procedure does not report potassium above a hemolysis index of 50.

What happened to this specimen, and what do you ask for?

TestResultPreviousReference intervalFlag
Potassium5.8 mmol/L4.1 mmol/L3 months ago3.5–5.1 mmol/LHigh

Specimen: H 240, L 10, I 1. Serum, syringe draw pushed through the needle into the tube

  1. Read the collection: a 25-gauge needle and a hard pull on the syringe.

    A narrow needle and a strong pull make blood rush through a tiny opening, and the force tears red cells apart.

  2. Follow the cells: many burst in the needle and spilled their potassium and hemoglobin into the specimen.

    Red cells hold far more potassium than plasma, so every broken cell adds potassium to the serum.

  3. Read the tube: the serum is pink-red, and the hemolysis index of 240 is far above the potassium limit of 50.

    Free hemoglobin colors the serum, and the analyzer's index measures how much is there.

  4. Ask for a new specimen: a wider needle, a gentle pull, and a transfer device to fill the tube.

    The damage came from the draw, so a careful collection gives a potassium that describes the patient.

The draw broke the red cells, so the potassium of 5.8 mmol/L describes the tube. Do not report it, and ask for a careful redraw.

Your turn

Problem 1 of 3

A visibly hemolyzed serum specimen gives a markedly elevated lactate dehydrogenase (LDH). The requesting service asks whether the patient is hemolyzing. What does the laboratory do?

Incorrect. Red cells broken during collection release their LDH into the specimen, so this result cannot show hemolysis in the patient.

Incorrect. Dilution brings the result into the measuring range, but the LDH released in the tube is still in it, so the rerun still reflects collection hemolysis.

Correct. A hemolyzed collection cannot show hemolysis in the patient, and liver disease, tissue injury, and ineffective erythropoiesis also raise LDH. Haptoglobin, indirect bilirubin, reticulocytes, and the film on a fresh specimen answer the question.

Hint
  1. Ask where the LDH in this tube came from.
  2. Red cells broken during the draw release LDH into the specimen.
  3. Ask which kind of specimen could show what is happening inside the patient.

Review Evidence of increased hemoglobin catabolism

Problem 2 of 3

A serum creatinine from a patient with jaundice has an icterus index above the method's creatinine limit. Yesterday's specimen was icteric too. The nurse offers to send a new specimen. What do you do?

The bilirubin comes from the patient, so a fresh specimen will be just as icteric. The redraw delays the result and repeats the interference.

Expected a redraw to clear a patient-related interference

Bilirubin from jaundice, lipid from severe hypertriglyceridemia, and hemolysis inside the patient appear in every specimen the patient gives, so a redraw repeats the interference and delays the result. A fasting redraw helps only when the lipemia came from a recent meal. Index limits, a blank, an alternate method, or ultracentrifugation work on the tube at hand.

The interference comes from the patient, so the answer lies with the tube at hand: the method's icterus limit, then the validated alternate method or other step the procedure names for icteric specimens.

Fasting helps when lipemia comes from a recent meal. It does not lower bilirubin from jaundice.

Hint
  1. Ask where the bilirubin in this serum comes from.
  2. The bilirubin is in the patient's blood, so it will be in the next tube as well.

Review Specimen integrity and interference

Problem 3 of 3

An adult woman's CBC fails the delta check against yesterday morning's. Her hemoglobin fell from 13.4 to 9.1 g/dL, and her MCV rose from 84.0 to 97.5 fL. QC is acceptable, and the specimen has no clot. What do you do first?

A matching rerun shows that the analyzer measured this tube consistently. It cannot show whose blood is in the tube.

QC and the clot check speak to the run and the tube. A specimen from another patient passes both, and releasing it would put someone else's values in her record.

Released a failed delta check without checking identity

A delta alert means the result differs from the patient's previous value by more than the laboratory's limit. A wrong-patient specimen, contamination, or a run problem can raise the same alert as a real change. Releasing before checking can place another patient's value in the record.

A person's MCV changes slowly, so a rise of 13.5 fL in one day points to another patient's blood in this tube. Infusion fluid would dilute the hemoglobin and leave the MCV unchanged. Identity is confirmed before the CBC goes out.

Review Analytic and postanalytic safeguards

Use it

  • An adult woman, 0204518, has a basic metabolic panel drawn at an outpatient clinic.
  • The collector noted a difficult draw by syringe.
  • The serum is red, and the analyzer reports a hemolysis index of 310.
  • Your procedure sets these hemolysis limits, and a result above its limit is not reported:
    • potassium at 50
    • creatinine at 500
    • sodium and chloride at 750
  • QC for the run is acceptable, and the label matches the order with both identifiers.
TestResultPreviousReference intervalFlag
Sodium139 mmol/L140 mmol/L30 days ago135–145 mmol/L
Potassium5.9 mmol/L4.2 mmol/L30 days ago3.5–5.1 mmol/LHigh
Chloride103 mmol/L102 mmol/L30 days ago98–107 mmol/L
Creatinine0.92 mg/dL0.90 mg/dL30 days ago0.59–1.04 mg/dL

Specimen: H 310, L 12, I 2. Serum, syringe draw transferred to the tube; collector noted a difficult draw

Decision 1 of 3

What best explains the potassium of 5.9 mmol/L?

Nothing here shows red cells breaking in the patient. The difficult syringe draw and the red serum explain a tube that was hemolyzed during collection.

Read a hemolyzed tube as hemolysis in the patient

Forceful aspiration, a narrow needle, or vigorous mixing breaks red cells in the tube and raises plasma hemoglobin, potassium, and LDH. Those changes describe the specimen. Reporting them as hemolysis in the patient starts a workup on an artifact. Haptoglobin, bilirubin, and reticulocytes on a properly collected specimen answer that question.

Red cells broken by the syringe draw release their potassium into the serum. The index of 310, six times the potassium limit, fits the rise from 4.2 mmol/L.

QC shows the analyzer measured its controls correctly. It cannot show whether the potassium in this serum came from the patient's plasma or from broken red cells.

Review Specimen integrity and interference

Decision 2 of 3

What do you do with the potassium?

Acceptable QC covers the analyzer. It cannot clear a specimen whose hemolysis index is six times the potassium limit, and the reported value would be the broken cells' potassium.

Released an unsuitable specimen's result because QC passed

Acceptable QC shows that the analyzer measured control material correctly. It cannot show infusion fluid, additive carryover, or hemolysis in this patient's tube. Releasing on that basis reports the effect of the contaminant or the broken cells as the patient's result.

Your procedure does not report potassium above its hemolysis limit, with or without a comment. A number from this tube would still reach the chart.

The index is far above the potassium limit and the hemolysis came from the draw, so a careful new collection is the way to a reportable potassium. Record the reason on the order.

A repeat measures the same hemolyzed serum and gives the same inflated potassium.

Review Specimen integrity and interference

Decision 3 of 3

What do you do with the sodium, chloride and creatinine?

Their hemolysis limits are well above 310, so hemolysis at this level does not change them enough to matter. Keeping them back delays results that are ready.

An index of 310 is below the limits for creatinine (500) and for sodium and chloride (750), and each result sits close to last month's. They can be released while potassium waits for the redraw.

The redraw is for potassium. These three results are below their own hemolysis limits and can be reported from this tube.

Review Specimen integrity and interference

The clue that settles it is the hemolysis index read against each test's own limit. At 310:

  • It is six times the potassium limit, so potassium needs a careful redraw.
  • It is below the limits for creatinine, sodium and chloride, so those three results are reportable from this tube.

The difficult syringe draw says the damage happened in the tube, which is why a redraw can fix it.

Keep